Evaluation of breath alcohol instruments II. In vivo experiments with Alcolmeter Pocket Model

The precision and accuracy of an Alcolmeter Pocket Model breath alcohol instrument have been investigated in experiments with human subjects under controlled conditions. The instrument response was zero in all tests with breath samples from alcohol-free subjects. The standard deviations of ethanol determinations in breath were ±0.0722 mg/ml during ethanol absorption and ±0.0416 mg/ml during ethanol elimination. The standard deviation during the elimination phase increased with ethanol concentration in the sample, being ±0.0416 mg/ml on average at a mean concentration of 0.420 mg/ml, corresponding to a coefficient of variation of 9.9%.The blood alcohol estimates using the Alcolmeter were somewhat too high during active absorption of ethanol, and too low during elimination, when a constant blood-breath alcohol ratio of 2100:1 was used to calibrate the instrument. During the elimination phase of ethanol kinetics and at a mean blood alcohol concentration of 0.50 mg/ml, the mean Alcolmeter result was 0.456 ± 0.169 mg/ml with 95% confidence, i.e. varying between 0.287 and 0.625 mg/ml 95 times out of 100 tests at this critical blood alcohol level.     

Post mortem markers of chronic alcoholism

We compared the post mortem diagnostic value of γ-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), alcoholic liver disease (ALD), blood alcohol concentration (BAC), the presence of multiple bruises and poor hygiene of the feet as markers of chronic alcoholism (heavy continuous drinking) in 32 alcoholics with 32 age-sex matched controls drawn from a forensic autopsy population. Alcoholics and controls were selected on the basis of positive and negative medical history but controls were excluded if BAC exceeded 70 mg%. Femoral venous blood, urine and vitreous humour alcohol concentrations were determined by headspace gas chromatography (GC). BAC was positive in 19 alcoholics (mean 234 mg%, range 2–570 mg%) and six controls (mean 32 mg%, range 2–52 mg%). Serum GGT was measured by a kinetic photometric method, and CDT by both isoelectric focusing/laser densitometry and by a commercial radioimmunoassay kit (CDTect^™). Features of alcoholic liver disease were graded histologically using two weighted scoring systems. Eleven alcoholics tested positive for GGT, CDTq and ALD, nine were positive for two tests, five for one test and three were negative for all three tests. No controls were positive for all three tests but six were positive for two tests and nine for only one test; 17 were negative for all three tests. Using the normal clinical cut-off values GGT, CDTq and CDTect^™ gave poor specificity which was improved at moderate cost to sensitivity by raising cut off values for each test. Comparison of receiver operating characteristic curves, likelihood ratios and post-test odds showed CDT to be the best individual test, followed by ALD and GGT. Quantitation of CDT by IEF/laser densitometry performed slightly better than MAEC/RIA by CDTect^™. CDT shows considerable promise as a post mortem marker of chronic alcoholism.     

血中酒精浓度的回推算研究

目的研究血中酒精浓度值（BAC值）的推算关系。方法对327位自愿受试者饮酒后测定其血中酒精时浓曲线进行分析,计算血中酒精清除率。结果血中酒精消除呈线性,327例血液中酒精消除线性相关系数为0.985±0.019,最小绝对值为0.98,最大绝对值1.000,消除斜率绝对值平均为（0.136±0.037）mg/mL/h,最小绝对值为0.075mg/mL/h,最大绝对值0.266mg/mL/h。结论血液中酒精浓度的推算可根据线性消除关系回推,血液中酒精浓度按照每小时下降0.10mg进行回推算。     

The effect of ibuprofen on ethanol concentration and elimination rate.

Pursuant to a recent driving under the influence (DUI) case, a medical study of six subjects was cited reporting that ibuprofen causes a decrease in the maximum rate of elimination of ethanol. Such a drug interaction is of significant forensic science interest and warrants further examination. This study investigates the effect of ibuprofen on ethanol elimination rate and ethanol concentration in nineteen volunteers. Volunteer subjects were randomly assigned to two groups administered either a placebo followed by ethanol or ibuprofen followed by ethanol. Subjects served as their own control. Blood ethanol concentrations were monitored every 30 to 60 min for up to 4 h with Intoximeter 3000 instruments. A blood sample was drawn at the final Intoximeter test and analyzed for ethanol and ibuprofen by gas chromatography and mass spectrometry, respectively. The mean elimination rate (+/- SD) as calculated using Widmark's elimination factor was 0.018 +/- 0.006 g/dL for ethanol and 0.017 +/- 0.007 g/dL/h for ethanol with ibuprofen. Mean ethanol concentrations (g/dL +/- SD) were: 0.095 +/- 0.026 (ethanol) and 0.095 +/- 0.033 (ethanol and ibuprofen) at 30 min; 0.077 +/- 0.026 (ethanol) and 0.075 +/- 0.031 (ethanol and ibuprofen) at 150 min; and 0.089 +/- 0.025 (ethanol) and 0.087 +/- 0.030 (ethanol and ibuprofen) overall. There was no statistically significant affect of ibuprofen on either the peak blood ethanol concentration or the ethanol elimination rate (p less than or equal to 0.001). These results reveal no evidence of a significant ethanol-ibuprofen interaction.     

The influence of sex hormones on the elimination kinetics of ethanol

The goal of the investigation was to research the influence of sex hormones on the elimination kinetics of ethanol. Forty-seven healthy men (average age 25+/-6.1 years) and 61 healthy women (average age 24+/-2.4 years) received 0.79-0.95g of ethanol/kg body weight in the form of an alcohol beverage of their choice. The target concentration for both sexes was a blood alcohol concentration (BAC) of 1.10g/kg. Blood samples for the determination of the ethanol concentration followed in the elimination phase in 10-20min intervals. The sex hormone levels (estradiol, progesterone and testosterone) were determined concomitantly from the serum. In men, the mean testosterone concentration was 5.3+/-1.6ng/ml, the mean estradiol concentration was 34.6+/-13.6pg/ml and the mean progesterone concentration was 0.9+/-0.3ng/ml. In women, the mean estradiol concentration was 47.6+/-52.6pg/ml and the mean testosterone concentration was 0.8+/-0.4ng/ml. Progesterone displayed a so-called dummy effect in women. In the high progesterone group (n=11), the mean concentration was 11.1+/-3.5ng/ml and in the low progesterone group (n=50) the mean was 0.6+/-0.3ng/ml. The mean hourly elimination rate (beta60) was 0.1677+/-0.0311g/kg/h in men. In women, the mean hourly elimination rate was 0.2044+/-0.0414g/kg/h in the high progesterone group and 0.1850+/-0.0276g/kg/h in the low progesterone group (p<0.05). The beta60 for women in the low progesterone group was significantly higher than that of the men, whose progesterone levels fell within a similar range (p>0.01). These results allow one to conclude that the gender differences in the pharmacokinetics of ethanol can partly, but not completely, be explained by progesterone levels.     

Alcohol metabolism of local Chinese in Hong Kong: a statistical determination on the effects of various physiological factors

A study was designed to examine the elimination rate of alcohol from the body of the local Chinese after consumption of different types of alcoholic drinks. The breath alcohol of 184 healthy volunteers was determined and converted into blood alcohol levels after they finished drinking. Information on the type and volume of alcoholic drinks consumed, age group, sex, drinking habit, and drinking on empty stomach or with/after meal was recorded for each participant. The results show that the elimination rate of an individual can be explained in terms of physiological variables including sex and drinking habit. The determined elimination rates allow forensic toxicologists to back calculate the blood alcohol concentration (BAC) of the drivers at the time of accident in drunk driving cases. The elimination rates of blood alcohol at 95% prediction intervals for male and female are in the range of 9.5-23.8 mg/100 ml/h and 11.1-37.1 mg/100 ml/h, respectively.     

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (IV) infusion over 45 min. After removing a mean fluid volume of 2.46±0.48 liters (±SD), span 1.76–3.43 liters by hemodialysis, the same subjects received a second IV infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05–1.10). The rate of ethanol disappearance from blood (β-slope) was faster (0.185±0.013 versus 0.157±0.022 g/l/h), the C₀ value was higher (0.79±0.08 versus 0.73±0.10 g/l) and the apparent volume of distribution (V_d) of ethanol was lower (0.507±0.049 versus 0.558±0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P<0.001) before dialysis (88.6±1.97 g/100 ml) compared with after dialysis (87.4±2.01 g/100 ml). The higher V_d for ethanol and lower C₀ as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (β-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.     

Postmortem absorption of drugs and ethanol from aspirated vomitus--an experimental model.

Using human cadavers an experimental model was developed to simulate the agonal aspiration of drug- and alcohol-laden vomitus. By needle puncture, an acidified (N/20 HCl) 60-ml slurry of drugs (paracetamol 3.25 g, dextropropoxyphene 325 mg) and ethanol 3% w/v was introduced into the trachea. After 48 h undisturbed at room temperature, blood samples were obtained from ten sites. Ethanol and drug concentrations were highest in the pulmonary vessels in all five cases studied. Pulmonary vein mean ethanol was 58 mg% (range 13-130), paracetamol 969 mg/l (range 284-1934), propoxyphene 70 mg/l (range 11-168). Pulmonary artery mean ethanol was 53 mg% (range 10-98), paracetamol 476 mg/l (range 141-882), propoxyphene 29 mg/l (range 7.6-80). Ethanol and drug concentrations in aortic blood were higher than in the left heart and concentrations in the superior vena cava were higher than in the right heart, suggesting direct diffusion into these vessels rather than diffusion via the pulmonary and cardiac blood. Potential interpretive problems arising from this phenomenon can be avoided by using femoral vein blood for quantitative toxicological analysis.     

Non-linear kinetics of ethanol elimination in man: Medico-legal applications of the terminal concentration-time data analysis

Research regarding parameters suitable for reporting on the activity of enzymatic systems responsible for ethanol metabolism is of obvious interest in medico-legal practice. Blood ethanol concentration-time curves, following oral administration of ethanol, have been developed for ethylic and non-ethylic subjects. This study has confirmed the non-linear kinetics of ethanol elimination; however, existing non-linear models appear to be inadequate for usual medico-legal practice, because of their complexity. We observed three phases during the elimination of ethanol. The first order terminal phase is characterized by its half-life. This parameter seems adequate as a basis for determining the activity of enzyme systems responsible for the metabolism of ethanol.     

甲基苯丙胺在家兔体内的毒物代谢动力学研究

目的研究甲基苯丙胺及其代谢物苯丙胺在家兔体内的毒物代谢动力学行为。方法GC/MS法测定家兔灌胃甲基苯丙胺后不同时间点血、尿中甲基苯丙胺和代谢物苯丙胺浓度,采用3P97程序进行房室模型拟合以及毒物代谢动力学参数计算。结果甲基苯丙胺和苯丙胺在家兔体内的毒物代谢动力学过程均呈一级动力学特征,符合二室开放模型。甲基苯丙胺在家兔体内Cm ax为1.457 mg/L±0.094 mg/L,Tm ax为1.557h±0.078h,t1/2 ka、t1/2α和t1/2β分别为0.384h±0.052h、1.614h±0.036h和3.007h±0.430h,CL为1.769 L/h/kg±0.114 L/h/kg。甲基苯丙胺的毒物代谢动力学方程为:C t=2.767 e-0.746 t+1.454 e-0.234 t+4.119 e-1.746 t。结论甲基苯丙胺在家兔体内吸收、消除和代谢都较快。建立的甲基苯丙胺毒物代谢动力学方程和参数可为甲基苯丙胺分析的合理取样、从血药浓度推断服毒时间以及甲基苯丙胺滥用的法医学鉴定提供理论依据。     

Evaluation of alcoholic intoxication depending of the level of brain ethanol-metabolizing enzymes in death from ischemic heart disease

Activities of alcohol dehydrogenases (ADG), aldehyde dehydrogenases (AlDG), and NADH+ dehydrogenases were measured by histochemical methods in neurons and capillaries of the gyrus cinguli and medulla oblongata of subjects dead from coronary disease. Enzymatic activities were found to depend on the stage of alcoholic intoxication. During resorption, characterized by reversible ethanol oxidation, the activities of AlDG and NADH+ dehydrogenases decreased, while during elimination the activities of these enzymes increased. ADG activity in cerebral tissue was increased during the entire period of alcoholic intoxication. The duration of alcoholic intoxication is determined by the amount of consumed ethanol and activity of AlDG. These regularities can be used for forensic medical evaluation of the role of alcoholic intoxication in coronary death.     

A kinetic model describing the pharmacokinetics of ethyl glucuronide in humans

The glucuronide conjugation is a minor pathway of ethanol metabolism. The determination of ethyl glucuronide (EG) in serum and urine has gained importance in forensic and other legal decisions. To prospectively calculate the serum concentration of this non-oxidative ethanol metabolite, the computer program developed includes a parameter fitting routine. Multiple ethanol doses can be handled.The mathematical modeling was based on the following assumptions and simplifications, respectively. A single enzyme system is responsible for ethanol conjugation at one distinct site; the distribution of EG into the systemic circulation is delayed; the elimination of EG follows first-order kinetics.The concentration of EG was calculated using three kinetic parameters: a rate constant for the first-order formation of EG from serum ethanol, a transfer constant for an obstructed transfer of EG from the formation site (FS) into the central compartment (CC) and an exponential elimination constant.The program was applied to the data collected from 21 drinking experiments. The fitting algorithm optimized the three kinetic parameters, until the sum of concentration error squares of the data points was minimized. The means+/-standard deviation of the rate constant for the first-order formation of EG from serum ethanol was 0.0011+/-0.0006 h(-1), the transfer constant for an obstructed transfer of EG from the FS into the CC was 0.43+/-0.1996 h(-1) and the exponential elimination constant was 3.0+/-1.45 h(-1).Using the range of these parameters, it is now possible to calculate minimum and maximum serum concentrations of EG based on ethanol doses and drinking times. The comparison of calculated and measured concentrations can prove the plausibility of an alleged ethanol consumption. This can be crucial when the serum ethanol concentration (SEC) itself is not meaningful.     

The influence of ethanol containing cosmetics on ethyl glucuronide concentration in hair

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE), non-volatile, direct metabolites of ethanol have been shown to be suitable markers for the evaluation of social and chronic excessive alcohol consumption. Previous investigations have shown that the regular use of hair-care products with high alcohol content lead to an increase of FAEE concentration and consequently gave false-positive results for the determination of FAEE in hair. In this study we investigated the influence of a long-term hair treatment with EtOH containing lotion, on the EtG concentrations in hair. In this study 7 volunteer subjects (classified as either rare, social or heavy drinkers) treated the right side of their scalp every day during a one or two month period with a commercial hair tonic (Seborin), which contains 44.0% ethanol (vol%). Collection of hair specimens from both sides of the scalp was done one day before hair treatment, one week and one month after treatment (for 5 subjects also after two months of treatment). A hair segment of 3 centimeters (cm) was cut and then washed with water and acetone, and then pulverized. EtG was quantified by GC/MS after pulverization and 2h of ultrasonication in water, extraction by solid phase extraction using Oasis MAX columns and derivatization with HFBA. Measurements were done in negative chemical ionization mode using EtG-D5 as internal standard. Comparison of EtG concentration in the treated and in the non-treated hair specimens did not show any increase at the different dates of collection for the 7 subjects. In conclusion, these results show that there is no indication for an increase of EtG after use of ethanol containing hair cosmetics.     

Comparison of ethanol concentrations in venous blood and end-expired breath during a controlled drinking study

Concentration-time profiles of ethanol were determined for venous whole blood and end-expired breath during a controlled drinking experiment in which healthy men (n=9) and women (n=9) drank 0.40-0.65 g ethanol per kg body weight in 20-30 min. Specimens of blood and breath were obtained for analysis of ethanol starting at 50-60 min post-dosing and then every 30-60 min for 3-6 h. This protocol furnished 130 blood-breath pairs for statistical evaluation. Blood-ethanol concentration (BAC, mg/g) was determined by headspace gas chromatography and breath-ethanol concentration (BrAC, mg/2l) was determined with a quantitative infrared analyzer (Intoxilyzer 5000S), which is the instrument currently used in Sweden for legal purposes. In 18 instances the Intoxilyzer 5000S gave readings of 0.00 mg/2l whereas the actual BAC was 0.08 mg/g on average (range 0.04-0.15 mg/g). The remaining 112 blood- and breath-alcohol measurements were highly correlated (r=0.97) and the regression relationship was BAC=0.10+0.91BrAC and the residual standard deviation (S.D.) was 0.042 mg/g (8.4%). The slope (0.91+/-0.0217) differed significantly from unity being 9% low and the intercept (0.10+/-0.0101) deviated from zero (t=10.2, P<0.001), indicating the presence of both proportional and constant bias, respectively. The mean bias (BAC - BrAC) was 0.068 mg/g and the 95% limits of agreement were -0.021 and 0.156 mg/g. The average BAC/BrAC ratio was 2448+/-540 (+/-S.D.) with a median of 2351 and 2.5th and 97.5th percentiles of 1836 and 4082. We found no significant gender-related differences in BAC/BrAC ratios, being 2553+/-576 for men and 2417+/-494 for women (t=1.34, P>0.05). The mean rate of ethanol disappearance from blood was 0.157+/-0.021 mg/(g per hour), which was very close to the elimination rate from breath of 0.161+/-0.021 mg/(2l per hour) (P>0.05). Breath-test results obtained with Intoxilyzer 5000S (mg/2l) were generally less than the coexisting concentrations of ethanol in venous blood (mg/g), which gives an advantage to the suspect who provides breath compared with blood in cases close to a threshold alcohol limit.     

Estimating the degree of ethanol intoxication from analysis of cerebro-cranial hematomas

314 cases of combined cerebro-cranial trauma and posttraumatic intracranial hematomas were identified of which ethanol was detected in 114 hematomas. The other investigative group was 103 hospitalized patients who had hematomas evacuated during neurosurgical procedures. In 62 of these cases ethanol was detected. Blood and urine samples were also collected and the alcohol concentration was determined in all specimens by GC and ADH. The ethanol elimination rate for autopsy and operative intracranial hematomas was approximately 0.07–0.08‰/h(±0.034‰/h). The elimination rate of ethanol from blood (β₆₀) was about two or three times greater as that from hematomas. Because of the different water content of intracranial hematomas from blood, it was necessary to adjust the ethanol concentration for water content. On the basis of the corrected ethanol concentrations and the elimination rates for both tissues it was possible to estimate the ethanol concentration at the time of injury. Intracranial hematomas are tissues of possible value in the determination of alcohol intoxication especially in alcoholism. Ethanol can be found in hematomas even after 72 h from head injury.     

Time of drug elimination in chronic drug abusers. Case study of 52 patients in a "low-step" detoxification ward

The elimination time of illicit drugs and their metabolites is of both clinical and forensic interest. In order to determine the elimination time for various drugs and their metabolites we recruited 52 volunteers in a protected, low-step detoxification program. Blood samples were taken from each volunteer for the first 7 days, daily, urine sample for the first 3 weeks, daily. Urine was analyzed using a fluorescence-polarization immunoassay (FPIA) and gas chromatography/mass spectrometry (GC/MS), serum using GC/MS. The elimination times of the drugs and/or their metabolites in urine and serum as well as the tolerance intervals/confidence intervals were determined. Due to the sometimes extremely high initial concentrations and low cut-off values, a few of the volunteers had markedly longer elimination times than those described in the literature. The cut-off values were as follows: barbiturates II (200ng/ml), cannabinoids (20ng/ml), cocaine metabolites (300ng/ml), opiates (200ng/ml). GC/MS detected the following maximum elimination times: total morphine in urine up to 270.3h, total morphine and free morphine in serum up to 121.3h, monoacetylmorphine in urine up to 34.5h, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in urine up to 433.5h, THC-COOH in serum up to 74.3h, total codeine in urine up to 123h, free codeine in urine up to 97.5h, total codeine in serum up to 29h, free codeine in serum up to 6.3h, total dihydrocodeine (DHC) in urine up to 314.8h, free DHC in urine up to 273.3h, total and free DHC in serum up to 50.1h. Cocaine and its metabolites were largely undetectable in the present study.     

Verbal Aggression Among Male Alcoholic Patients and Their Wives in the Year Before and Two Years After Alcoholism Treatment

Our earlier reports on 88 male alcoholics and their wives showed that domestic violence decreased significantly in the first and second year following a behavioral marital therapy (BMT) alcoholism treatment program. The present study examined verbal aggression in this same sample. In the year before BMT, verbal aggression was significantly greater—being five to seven times more prevalent for clinically elevated aggression and substantially more frequent—for the alcoholic husbands and their wives than for a demographically matched, nonalcoholic comparison sample. In the two years after BMT, both alcoholic men and their wives showed significant and substantial reductions in verbal aggression as compared with the year before BMT. Despite these significant reductions from the year before BMT, verbal aggression in the two years after BMT remained significantly elevated relative to demographically similar nonalcoholic controls. As predicted, relapsed alcoholics and their wives showed more verbal aggression in the 2 years after BMT than both couples with a remitted alcoholic husband and demographically similar nonalcoholic controls, whereas remitted alcoholics and their wives had similar levels of verbal aggression to the nonalcoholic controls. Further, frequency of drinking was positively correlated with verbal aggression in the 2 years after BMT; verbal aggression was greater when the alcoholic husband drank more frequently.     

The influence of alcohol content variation in UK packaged beers on the uncertainty of calculations using the Widmark equation

It is common for forensic practitioners to calculate an individual's likely blood alcohol concentration following the consumption of alcoholic beverage(s) for legal purposes, such as in driving under the influence (DUI) cases. It is important in these cases to be able to give the uncertainty of measurement on any calculated result, for this reason uncertainty data for the variables used for any calculation are required. In order to determine the uncertainty associated with the alcohol concentration of beer in the UK the alcohol concentration (%v/v) of 218 packaged beers (112 with an alcohol concentration of ≤5.5%v/v and 106 with an alcohol concentration of >5.5%v/v) were tested using an industry standard near infra-red (NIR) analyser. The range of labelled beer alcohol by volume (ABV's) tested was 3.4%v/v – 14%v/v. The beers were obtained from a range of outlets throughout the UK over a period of 12?months. The root mean square error (RMSE) was found to be ±0.43%v/v (beers with declared %ABV of ≤5.5%v/v) and ±0.53%v/v (beers with declared %ABV of >5.5%v/v) the RMSE for all beers was ±0.48%v/v. The standard deviation from the declared %ABV is larger than those previously utilised for uncertainty calculations and illustrates the importance of appropriate experimental data for use in the determination of uncertainty in forensic calculations.     

Endogenous methanol: variability in concentration and rate of production. Evidence of a deep compartment?

The endogenous methanol concentration was determined in 72 men aged between 18 and 35 years in the morning after a 12-h period of fasting and abstinence from alcohol. The distribution curve was found to be skewed to the right, the concentrations ranging from ‘0’ (below the detection threshold) to 3.4 mg/kg. The median was 0.1 mg/kg and the mean 0.35 mg/kg. Significant differences were found between three groups defined according to the duration of prior abstinence from alcohol (8 h, 30 h, and 5 days). The highest values were seen after the shortest period of abstinence and the lowest values after the longest period of abstinence. The course followed by the methanol concentration in the presence of blocking of methanol oxidation by orally or parenterally administered ethanol was observed over at least 10 h on two separate occasions in a further 8 subjects aged between 24 and 35 years. At blood ethanol concentrations of more than 0.20 g/kg, the rate of production of methanol, calculated by regression, ranged from 0.09–0.37 mg/kg/h (r = 0.970–0.554, S_y,x = 0.227–0.565 mg/kg). The rise in methanol concentration at the start of ethanol administration was significantly more rapid than the subsequent rise. It is hypothesised that there may be a so-called deep compartment for methanol that would explain the dependence of the endogenous methanol level on the duration of the preceding period of abstinence from ethanol, and the occurrence of an initial phase of faster rise in methanol concentration associated with the administration of ethanol.